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SARS-CoV-2 BA.4/5 infection triggers more cross-reactive FcγRIIIa signaling and neutralization than BA.1, in the context of hybrid immunity.

Simone I RichardsonNonkululeko MzindleThopisang MotlouNelia P ManamelaMieke A van der MeschtBronwen E LambsonJosie EverattDaniel Gyamfi AmoakoSashkia BallaAnne von GottbergNicole WolterZelda de BeerTalita Roma de VilliersAnnie BodensteinGretha van den BergFareed AbdullahTheresa M RossouwMichael T BoswellVeronica UeckermannJinal N BhimanPenny L Moore
Published in: Journal of virology (2024)
The continued evolution of SARS-CoV-2 has resulted in a number of variants of concern. Of these, the Omicron sublineage is the most immune evasive. Within Omicron, the BA.4/5 sublineage drove the fifth wave of infection in South Africa prior to becoming the dominant variant globally. As a result this spike sequence was approved as part of a bivalent vaccine booster, and rolled out worldwide. We aimed to understand the cross-reactivity of neutralizing and Fc mediated cytotoxic functions elicited by BA.4/5 infection following infection or breakthrough infection. We find that, in contrast to BA.1 which triggered fairly strain-specific antibodies, BA.4/5 triggered antibodies that are highly cross-reactive for neutralization and antibody-dependent cellular cytotoxicity potential. Despite this cross-reactivity, these antibodies are compromised against highly resistant variants such as XBB.1.5 and BQ.1. This suggests that next-generation vaccines will require XBB sublineage immunogens in order to protect against these evasive variants.
Keyphrases
  • sars cov
  • south africa
  • copy number
  • gene expression
  • magnetic resonance imaging
  • risk assessment
  • zika virus
  • coronavirus disease
  • hiv infected
  • drug administration